It has been shown in pre-clinical and clinical bioavailability models that administration of ACC resulted in an enhancement of calcium bioavailability (Meiron et al., J Bone Miner Res. 2011, 26(2):364-72, Shaltiel et al., Health 5, 2013, 18-29, and Vaisman et al., Journal of Bone and Mineral Research, 2014, 29 (10), pp 2203-2209), an effect which is especially important in relieving calcium malabsorption related conditions and disorders. Oral administration of ACC led to a positive effect on bone parameters, demonstrated by antiresorptive action, anabolic effects and maintenance of bone mechanical strength in an osteoporosis prevention model (Shaltiel et al.). WO 2013/088440 discloses amorphous calcium carbonate compositions for use in treatment of calcium malabsorption and malabsorption associated disorders, diseases and conditions, and for increasing bone mineral density in calcium malabsorption and bone metabolism associated disorders.
WO 2005/115414 describes orally administrable compositions comprising stable ACC as well as method for treating osteoporosis, osteomalacia and related diseases. WO 2008/041236 describes formulations containing amorphous or microcrystalline calcium carbonate which are efficient in treating various pathological conditions including proliferative diseases, neurological disorders and muscoloskeletal disorders. WO 2009/053967 describes compositions containing amorphous calcium carbonate (ACC), and at least one phosphorylated amino acid or phosphorylated peptide. Said compositions may be used for treatment of various diseases listed therein.
Nerve injuries are common in clinical practice. There are many examples where damage of peripheral nerve, caused by accident or the like, is unable to be completely restored. There are also many clinical examples where peripheral nerve must be excised as a result of surgical operations in general. While the central nervous system (CNS) has a long and a weak self-repair of nerve fiber, the peripheral nervous system (PNS) has the ability for nerve repair by rapid nerve fiber regeneration. Studies on the recovery of PNS functionality after injury have become a rapidly growing field dedicated to the searching of suitable ways for facilitate and guide axonal regeneration.
Various approaches have been developed in an attempt to regenerate injured peripheral nerves. One such technique involves the actual suturing of the proximal and distal ends of the severed nerve. The use of various conduits, sutured in between the proximal and distal nerve stumps, for the guidance of the severed regenerated axons has been actively pursued.
Additional diseases that currently lack sufficient treatment relate to a muscular dystrophy. Muscular dystrophy is a group of muscle diseases that weaken the musculoskeletal system and hamper locomotion. Muscular dystrophies are characterized by progressive skeletal muscle weakness, defects in muscle proteins, and the death of muscle cells and tissue. One of such diseases is Duchenne muscular dystrophy (DMD), a lethal muscle wasting disease affecting approximately one in 3500 boys. Duchenne boys have a limited life expectancy of approximately 20 years. The disorder is caused by mutation in the dystrophin gene; many different mutations have been identified as leading to dysfunction of the protein dystrophin. It is characterized by progressive skeletal muscle wasting and degeneration (Shin et al., Int J Biochem Cell Biol. 2013, 45(10):2266-79), which also involves abnormal calcium homeostasis. Medical management of the muscular dystrophies has included the use of corticosteroids; however, despite their considerable beneficial effects, prolonged treatment with corticosteroids can lead to osteoporosis. Even without corticosteroids Duchenne muscular dystrophy leads to reduced mobility, which is associated per se with an increased chance of fractures and reduced bone mineral density (Nanette et al., Phys Med Rehabil Clin N Am. 2012, 23(4):773-99).
Currently, no satisfactory treatment for DMD or to nerve injury is present nowadays, and reducing the severity of symptoms and improving the quality of life patient suffering from these conditions can be considered as an achievement.
The area of assisted reproductive technology (ART) is aimed at solving the problem of both male and female infertility. One of the main techniques is in vitro fertilization (IVF). The content of the cell culture media may significantly influence the fertilization and embryonic development and thus consequently the outcome of the procedure. The success rate of IVF is mainly related to the number of embryos transferred as well as factors such as embryo quality. Changing the culture media may significantly influence the in vitro embryo development. As elevating the quality of embryos and the number of embryos reached advanced developmental stage may increase the chances for successful conception, finding the optimal conditions for in vitro embryo development can increase the efficiency of the whole IVF process.
“Male factor” infertility is seen as an alteration in sperm concentration and/or motility and/or morphology in at least one sample of two sperm analyzes, collected 1 and 4 weeks apart. In humans, it accounts for 40-50% of infertility and affects approximately 7% of all men. Male infertility is commonly due to deficiencies in the semen or semen quality reflected in low sperm count, motility, and abnormal morphology of sperm (Kumar and Singh, 2015, J. Hum. Reprod. Sci., 8(4): 191-196).
Most techniques of ART, such as Intrauterine Insemination or conventional IVF require at least normal motility of sperm. Several methods for sperm selection are present nowadays, for example a classical washing swim-up technique is used to select the most motile cells based on the natural sperm motility. The selected sperm may be consequently used in the IVF procedure. Numerous techniques for in vitro sperm amelioration were suggested. The results of in vitro experiments suggest that vitamin E may protect spermatozoa from oxidative damage and loss of motility as well as enhance the sperm performance in the hamster egg penetration assay (Agarwal & Sekhon, Human Fertility, December 2010, 13(4): 217-225). Bhoumik et al., (Cell Biochem. Biophys., 2014, 70: 1177-1183) demonstrated that addition of Ca2+ ions to calcium-free mediums increases forward sperm motility up to 20%.
The phenomena of male infertility is increasing worldwide (Kumar and Singh) with more and more couples turning to Assisted Reproductive Technology. Thus, novel methods for improving sperm motility in vitro are required.